At present, therapy of osteoarthritis is symptomatic rather than systematic. This has resulted from a fundamental lack of understanding of the basic causes of the disease. Because increasing numbers of individuals are living longer, the impact of aging on the incidence of osteoarthritis has become more than ever an important health problem, and at least 20% of elderly people have a severe disability due to osteoarthritis requiring surgical intervention. Although osteoarthritis is seen most frequently in the aged population, it is not clear whether the aging process and osteoarthritic pathology are causally related. The proposed research is designed to address a basic question with regard to osteoarthritis pathogenesis; that is, Are changes in articular cartilage associated with osteoarthritis seen in aged cartilage free of osteoarthritic pathology? and, Are the changes osteoarthritic cartilage metabolism irreversible or can disease progression be retarded? A basic understanding of cartilage metabolism in young normal, aged and osteoarthritic cartilage should help provide ways for approaching a more systematic therapeutic modality in treating osteoarthritis.